The thaumatins are a family of plant-derived proteins with a sweet taste many thousand-fold more intense than sugar. XOMA has purified and sequenced the two major plant proteins and in an effort to improve taste quality, has generated more than 100 thaumatin variants. Most of these have been produced in test amounts via a yeast secretion system. Cryschem is solving the three-dimensional structure of plant thaumatin by X-ray analysis. The structures of thaumatin variants having improved taste properties will then be determined with special emphasis placed on understanding conformational features in regions shown by XOMA's taste tests to affect sweet taste. Little is known about the molecular mechanism by which thaumatin is able to elicit an organoleptic response. We are in a position to elucidate those structural features important for receptor binding by using a number of our genetically engineered sweet proteins. Thaumatins having high affinity for taste receptors in human taste tests and primate neurophysiological assays will be used to isolate receptors from primate tongue tissue extracts. Attempts will be made to identify the site(s) of interaction. The combination of structural information with receptor binding studies and quantitative primate taste tests should allow us to design a second generation of protein sweeteners with specific taste and stability characteristics.